When faced with a terminal illness, the last thing anyone wants to hear is that the medical establishment has nothing left in its arsenal to help you. Yet, for so many patients, this is precisely the case, and with no alternatives in front of them, many are tempted to try the unorthodox and the unproven.

To some extent, medical tourism is built on that desperation; the hope that a treatment that has not found domestic approval might yet be worth a try somewhere else—locations where regulations aren’t as strictly enforced, perhaps.

With the recently signed Right-to-Try legislation, however, these patients might have another option. Rather than spend their remaining few dollars on travel to distant lands, they can spend that money at home, paying out of pocket for experimental therapies-on-demand, if those treatments have passed Phase 1 clinical trials.

The patient doesn’t have to enroll in the drug company’s clinical trials to receive therapy, and the results of right-to-try treatment will not be used in regulatory review of the treatment for ultimate approval.

If we set aside the cost issue for a moment, this seems like a wonderful opportunity for patients who see the risk of death as more worrisome than the risk of adverse events. And it indemnifies the drug companies from the risk of having their experimental therapeutics tagged with negative outcomes from uses they likely never intended.

There is, however, another perspective.

In May, I questioned the clinical and scientific utility of single-arm clinical trials, suggesting that without a comparator (e.g., placebo or standard of care), there could be no statistical understanding of the resulting data.

A counter-argument for that could be that the sheer numbers of patients achieving similar results suggests that something was happening, and if most of those responses were positive, was that not a good thing?

In the more distant past, I also questioned the validity of off-label prescribing of approved drugs. To me, clinicians were holding unregulated clinical trials based on personal prescribing experience with a treatment, clinical hearsay in the form of case studies or logic exercises based on suspected modes of action.

Again, the counter could be that because the treatment has already been approved, even if not for this specific patient population, it has been well characterized through numerous clinical trials and post-marketing monitoring. Thus, the relative risk profile of receiving treatment is largely known and the clinician can make a well-informed decision about the risk to his or her patient.

What is being proposed through Right-To-Try, however, invalidates both counter-arguments.

Rather than offering whatever statistical validity comes from sheer numbers of participants, when the patient exercises his or her right-to-try, N = 1. Thus, whatever happens once treatment starts offers essentially zero scientific or clinical insight.

And because treatment is being given with a drug that has likely not been tested on very many people even if it has passed Phase 1 testing, the risk profile is still largely unknown. Just look at the numbers of drugs that fail post-Phase 1 or even post-approval due to safety concerns.

Again, I understand that for the patient who is facing death, none of this likely matters.

If the treatment fails, it doesn’t change the patient’s outcome; but if it positively impacts the disease course and extends the patient’s life, it was worth the risks.

All of this should matter, however, to those in the healthcare, drug and allied industries.

Even if these patients are being given Right-To-Try experimental treatments outside of the patient selection processes, should we not still try to learn everything we can from that treatment of that patient?

In choosing to participate in a “clinical trial of one,” should the patient not be expected to participate in the same scientific analysis as patients who enroll in clinical trials of dozens, hundreds or thousands?

If the treatment fails, then perhaps we can learn something that helps us better select other patient populations. If the treatment succeeds, then we may have the basis of future trials and other indications.

But without examining endpoints and biomarkers, without profiling patient -omics, without monitoring metabolic chemistries and adverse events, the failure or success of treatment stands as completely meaningless to the scientific and clinical communities.

I appreciate that what I am suggesting would require great clarity on a variety of fronts, not the least of which is corporate and medical liability of having such information. But how is that ultimately different from the clinical trials process as it stands?

The hope of experimentation is to better understand the situation after the experiment than you did before it.